Process for crimping an artificial implant for use in an animal body



United States Patent Ofifice 3,284,557 Patented Nov. 8, 1966 3,284,557 PROCESS FOR CRIMPING AN ARTIFICIAL IM- PLANT FOR USE IN AN ANIMAL BODY Seymour Polansky, Somerville, N.J., assignor to Ethicon, lino. Sonnet-ville, N..l'., a corporation of New Jersey No Drawing. Filed Dec. 20, 1962, Ser. No. 246,002 2 Claims. (Cl. 264238) The present invention has to do with artificial vascular parts for an animal body, including humans; and to a process for forming such parts.

For purposes of clarity, the terms used 'herein are defined as follows:

Tendon collagen fibril means a thread-like collagen structure derived from beef tendon that is round in crosssection. These fibrils in the completely dehydrated state measure about 500 to 2,000 Angstroms in diameter.

Swollen tendon collagen fibril means a collagen fibril derived from beef tendon that has been swollen in acid solution. The diameters of swollen collagen fibrils range from less than 5,000 Angstroms to about 90,000 Angstroms.

Monofilament means a single thread of oriented collagen fibrils as extruded through a single orifice in a spinnerette.

Multifilament means a group of individual separate collagen monofilaments extruded through a spinnerette. Further details are provided in related application Serial No. 216,247, filed August 10, 1962.

Strand means a group of collagen monofilaments that have been united to form a unitary structure.

Non-absorbable fiber means those fibers, synthetic or natural, which are not absorbed by an animal body, particularly a human body, when present therein over an extended period of time. A non-absorbable fabric is a fabric formed of non-absorbable fibers.

Associations of collagen and non-absorbable fibers means a combination of collagen filaments or strands and one or more non-absorbable fibers, formed by weaving, knitting, braiding, crocheting, etc. the filaments or strands and fibers together into articles, including tubes, which can be straight or Y-shaped.

Crimping means causing to contract into ridges or folds, bend or twist, so as to give a wavy or corrugated form to an article, particularly a tube.

Set means to establish or fix in a desired position or pattern.

During the past decade, considerable attention has been given to development of artificial vascular parts or grafts as implants for animal bodies. Synthetics such as Vinyon-N, nylon, Orlon, Dacron, Teflon and Ivalon have been woven and knitted into tubes and other suitable shapes, for use as arteries, veins, ducts, and the like. It has been recognized that an artificial graft must meet a number of standards in order to be of value. In particular, the graft must have certain physical properties such that it can be readily handled and manipulated during the specific surgery calling for its use. It must be flexible, for such is essential during an operation when time is critical and the graft must be accommodated to the artery, vein or the like to which it is being secured. It is sometimes necessary in surgery to bend a device or graft either around or under a body organ. An essential feature is that the graft be crimped to allow for flexing with out collapse and closing of the lumen thereof. If the graft were not crimped, there is ever present the danger that when bent or flexed acutely in the body, the lumen would collapse, leading to fatality. A crimped configuration also allows for any length adjustment of the graft during healing of the body and for any body movement.

Crimping of artificial grafts has been accomplished by heat setting of nylon and Teflon tubes, as described by Edwards in Surgery, vol. 45, No. 2, pages 298-309, February 1959. Dacron tubes have been held in crimped form and then subjected to steam (250-260 F.) at 15- 20 p.s.i. for 10 to 30 minutes, to set the tubes in crimped configuration (DemsykU.S. Patent No. 2,990,605). Dacron tubes have also been set after being crimped when baked on a mandrel at about 360 F. for nine minutes (Starks-3,029,819). However, such conditions cannot be used advantageously with collagen, collagen-Dacron, collagen-Teflon grafts and others in which collagen is associated with a non-absorbable fabric. The conditions mentioned above for setting of a crimped tube of nylon or Dacron, are unsatisfactory for collagen.

Collagen grafts and grafts comprised of collagen and non-absorbable fibers have recently been developed, and are described in application Serial Number 92,620, filed March 1, 1961. These grafts are far superior torelated gra fts consisting only of non-absorbable fibers such as Teflon and Dacron, since the host tissue which completely replaces the collagen is completely integrated with the non-absorbable fiber. Furthermore, the non-iabsorbable fiber gives strength to the grafted areas. However, one problem has been that of developing a technique to establish a set crimped configuration in tubes Olf collagen and associations of collagen and non-absorb-able fibers. It has been found that conditions employed earlier for imparting a crimped configuration to tube formed of non-absorbable fibers are unsatisfactory for the tubes described in the pending application referred to above, and those described herein.

It is an object of this invention, therefore, to provide a process for forming artificial vascular parts for an animal body, the parts being characterized by crimped configura tion, elasticity and a lurnen which remains open even when the part is flexed acutely; that is, the parts are nonkinkinig when flexed. It i another object to provide a process for forming collagen and associations of collagen and non-absorbable fibers in crimped configuration. Still another object is to provide crimped grafts of collagen and of associations of collagen and non-absorbable fibers in which the collagen has not been degraded extensively. A further object of the invention is to set grafts of collagen =and of associations of collagen and n-on-absorbiable fibers in crimped configuration. Still other obpe-cts of the invention will appear from the following description.

The fongoing objects are realized by crimping a tube composed of beef tendon collagen, which said collagen has been purified by enzymatic removal of el astin followed by acid swelling, or a tube formed of fibers of such enzyrne treated beef tendon collagen and one or more nonabsora-bable fibers, and setting the crimped tube. Setting is accomplished by any one of several related treatments described herein. The product so obtained has a cor r-ugated configuration and is flexible and longitudinally elastic.

Examples of suitable non-absorbable fibers for use herein are Vinyon'N, a resin manufactured by The Carbide and Carbon Corporation by copolymerizing vinyl chloride and acryloni-trile; Saran, a vinyl chloride polymer manufactured by the Dow Chemical Company; nylon, a polyamide resin made by polymerization of the hexamethylene diarnine salt of adipic acid; Orlon, a synthetic fiber made from .polyacrylonitrile; Dacron, a synthetic fiber made from terephthalic acid and ethylene glycol; Teflon, a tetrafluoroethylene polymer; poly'olefins such as polyethylene and polypropylene; cotton and silk. Nylon, Orlon, Dacron and Teflon are made by the E. I. du Pont de Nemours & Company. Dacron and Teflon are particularly preferred herein because both have displayed excellent retention of tensile strength over long periods of time and both are essentially inert, Teflon being slightly more inert and slightly stronger than Dacron. Other preferred fibers are polyolefins.

As indicated above, tubes woven, knitted, braided, crocheted, etc. from collagen filaments, or from the said filaments and non-absorbable fibers, are already known. Since they are described at length in related application Serial Number 92,620, filed March 1, 1961, detailed description is not given herein. Reference is made to the said application for said details.

Tubes woven, knitted, braided, crocheted, etc., as referred to above, can be crimped in shape 'for the setting contemplated herein. They may be crimped when a mandrel-a smooth rod-is inserted therein, the mandrel being of external diameter slightly less than that of the tube. The tube can then be crimped by forcing the ends thereof toward each other, in preparation for one or more of the treatments of this invention. Still other known techniques for crimping a fiber tube can be used herein. For example, a mandrel can be inserted through a fiber tube, and a thread can be wound about the tube in a suitable pattern, as in the form of a helix or double helix, and then the ends of the tube can be forced toward each other. This is followed by any one of several particular treatments. It is to be understood, therefore, that all techniques for crimping a tube in preparation for setting are contemplated for use herein. Since such techniques have already been illustrated by Edwards, Demsyk, Starks and others, it is considered unnecessary to illustrate the same with drawings.

The particular procedures used herein to set a tube comprised of collagen or of an association of collagen filaments and of non-absorbable fibers are the following:

(1) Heating a crimped tube with steam under a pressure from about to about 18 p.s.i.g., for an approximate period of time of 1 to 20 minutes, and then drying the tube;

(2) Heating a crimped tube in water at a temperature from about 40 C. to about 100 C. for between about 1 and about 20 minutes, and drying the tube;

(3) Tanning a crimped tube by contacting the same with a tanning solution, and drying; and

(4) Heating a crimped tube formed from collagen (with or without non-absorbable fibers) having a water content of at least about 10 percent by weight at a temperature between about 140 and about 160 C. for 5 to 20 minutes.

Of the several procedures enumerated above, (3) is particularly preferred in view of the advantageous properties obtained therewith.

Other suitable techniques for setting a crimped tube include subjecting the said tube to: radiation, and ultra violet light.

While satisfactory results have been realized with techniques (1) through (4) above, several closely related techniques have proven to be completely unsatisfactory. By way of illustration, when a tube is held in crimped configuration, then wet with water and dried, a permanent crimping is not imparted. Similarly, a tube wet with water, followed by crimping on a mandrel and drying, does not hold a crimped configuration; it becomes limp and collapses when bent. Another failure resulted when a tube was tanned, followed by crimping on a mandrel; again, a permanent crimp was not imparted to the tube.

The present invention is more fully described and exemplified in the following examples and related discussion. It is to be understood, however, that my invention is not to be limited to any specific form of materials or conditions set forth in the examples, but is limited solely by the description in this specification and the appended claims. Throughout the specification and the examples which follow, all quantities are expressed in parts by weight unless otherwise specified.

' Example 1 A tube crimped on a mandrel was held in an autoclave for 12 minutes. The pressure in the autoclave was about 12 p.s.i.

In this example, a 6-inch tube was used. The tube had a diameter of 10 mms. and the mandrel upon which it was crimped had a diameter of about 9 mms.

The tube was a plain weave (one up and one down) of Dacron and collagen yarn. Collagen multifilament yarn, 190 denier, 18 ends (7 /2 Z) and Dacron multifilament yarn, 70 denier, 34 ends (5 Z) are twisted together (1 turn S ply) and used for the warp and filling. The tube is woven using a reed 28, 5 ends per dent, with 97 warp yarns and 70 picks per inch.

The tube was used for a thoracic implant in a dog. The implant continues to function after 7 months in the animal.

Example 2 A tube (identical to the one in Example 1) crimped on a mandrel was immersed in a large excess of water, at a temperature of 50 C. for 5 minutes, and was then dried. The tube was removed from the mandrel. When rewet with water, the tube lost very little elasticity and, when bent acutely, an open lumen was maintained. These characteristics were exhibited satisfactorily after several wetting and drying cycles.

Example 3 A tube (identical to the one in Example 1) crimped on a mandrel was treated with a large excess of an aqueous tanning solution comprising 1 part of formaldehyde, chromium sulfate equivalent to 0.4 part of chromic oxide, followed by a solution of 0.5 part of pyrogallol and 0.6 part of Na S O The tube was then dried and the mandrel removed therefrom. The characteristics of the tube were similar to those of the crimped tube obtained in Example 2.

An advantageous feature of setting the tube in crimped configuration by this tanning technique is avoidance of any collagen degradation. There is no need to heat the tube during the tanning procedure.

A 2 inch sample of this tube was stretched to 2 inches and was implanted as an abdominal graft in a dog. The surgical procedure was without incident. The graft remains patent after three months.

It is to be understood that any of the known tanning agents for use with collagen can be used herein. Chromium, formaldehyde, polyhydroxyphenols, etc. can be used alone or in combination. Particularly preferred herein, however, are the tanning procedures described in related applications Serial Numbers 85,289 and 85,302, both filed January 27, 1961.

Several tubes prepared as indicated in the foregoing examples, and others prepared in other manner, were subjected to a series of tests. The capacity of the tubes to stretch when wet was measured by immersing a set, crimped tube in water at 25 C. for 15 minutes, the tube being measured before immersion and, while wet, following immersion. The permanence of set was measured by suspending a 100 gram weight from one end of a suspended t be (crimped set) for 15 minutes; allowing the tube to relax and promptly measuring it. Permanent set is represented by:

stretch out length initial length Results of the tests are given below in Table 1.

permanent set percent X 100- 100 While results shown above for the first four tubes, contemplated herein, reveal that such tubes have desirable properties, the results reveal a substantial superiority for the tanned tube of Example 3.

As indicated above, the crimped articles formed by the process described herein are useful as vascular grafts. They have desirable characteristics as revealed by their maneuverability, flexing quality and capability of maintaining an open lumen when flexed acutely.

Since the crimped articles of this invention contain collagen which is absorbable in the body and are, therefore, porous during use therein, artificial esophagi and trachea are not included herein. Such artificial articles should be substantially non-porous when in the body.

While the invention has been described in detail according to the preferred method of carrying out the process and yielding the products, it will be obvious to those skilled in the art, that changes and modifications can be made (without departing from the spirit or scope of the invention) and it is intended in the appended claims to cover such changes and modifications.

I claim:

1. The process of forming an artificial implant which is elastic and non-kinking when flexed comprising the steps of: I

crimping a tube composed of beef tendon collagen which said collagen has been purified by enzymatic removal of elastin followed by acid swelling;

setting the tube while in the crimped condition with Water at a temperature of from 40 C. to C. for between about one and about 20 minutes; and, drying the crimped tube.

2. The process for forming an artificial implant which is elastic and non-kinking when flexed, comprising the steps of:

forming a tube containing a substantial quantity of collagen fibers associated with one or more synthetic organic polymer fibers;

inserting within said tube a mandrel, the external diameter of which is slightly less than the diameter of the tube;

crimping the tube on the mandrel;

setting the crimped tube while on the mandrel by contacting it with water at a temperature from 40 C.

to 100 C. for between about one and 20 minutes; drying the tube while in the crimped condition; and, removing the mandrel.

References Cited by the Examiner UNITED STATES PATENTS 2,637,321 5/1953 Cresswell 128-335.5 2,836,181 5/1958 Tapp.

2,900,644 8/1959 Rosenberg et al. 128-334 XR 3,029,819 4/1962 Starks 128-334 3,034,852 5/1962 Nishihara 264-202 3,093,439 6/1963 Bothwell 128-335.5 XR 3,105,492 10/1963 Jeckel 128-334 3,108,357 10/1963 Liebig -139-387 X 3,114,593 12/1963 Griset et al 264103 3,155,095 11/1964 Brown 128-334 OTHER REFERENCES A.P.C. Application of Freudenberg, Serial No. 313,138, Pub. April 1943.

Bogue: The Chemistry and Tech. of Gelatin and Glue, McGraw-Hill, N.Y. (1922), pp. 49-52.

Wesolowski et al.: Surgery, July 1961, pp. 9196.

ALEXANDER H. BRODMERKEL, Primary Examiner. DONALD W. PARKER, Examiner.

A. I. SMEDEROVAC, F. S. WHISENHUNT,

Assistant Examiners. 

1. THE PROCESS OF FORMING AN ARTIFICIAL IMPLANT WHICH IS ELASTIC AND NON-KINKING WHEN FLEXED COMPRISING THE STEPS OF: CRIMPING A TUBE COMPOSED OF BEEF TENDON COLLAGEN WHICH SAID COLLAGEN HAS BEEN PURIFIED BY ENZYMATIC REMOVAL OF ELASTIN FOLLOWED BY ACID SWELLING; SETTING THE TUBE WHILE IN THE CRIMPED CONDITION WITH WATER AT A TEMPERATURE OF FROM 40*C. TO 100*C. FOR BETWEEN ABOUT ONE AND ABOUT 20 MINUTES; AND, DRYING THE CRIMPED TUBE. 